To assess the feasibility and efficacy of Carfilzomib in combination with Thalidomide and Dexamethasone in a phase II trial.
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To establish the response, in patients with Multiple Myeloma at first
presentation, to carfilzomib in combination with thalidomide and dexamethasone.
Secondary outcome
To investigate the clinical efficacy and toxicity of carfilzomib in combination
with thalidomide and dexamethasone in remission induction of Multiple Myeloma
at first presentation.
To investigate the clinical efficacy and toxicity of carfilzomib in combination
with thalidomide and dexamethasone in consolidation treatment of Multiple
Myeloma at first presentation.
To assess the stem cell harvest following carfilzomib in combination with
thalidomide and dexamethasone.
To assess Progression-free survival (PFS).
Background summary
Thalidomide and bortezomib combined with dexamethasone and a third agent
(alkylating agent or anthracycline) are now recognized as the most active drugs
for remission induction in transplant candidates. In elderly patients they are
combined with Melphalan/Prednisone (MP) in first line treatment. Both drugs
share the disadvantage of inducing peripheral polyneuropathy which is dose
limiting in 50% of patients and leads to premature termination of treatment in
25%.
Replacing bortezomib by carfilzomib would associate effective proteasome
inhibition with lack of neuropathy, thereby improving the proportion of
patients who are able to complete the planned treatment and reducing the rate
of serious adverse events, in particular polyneuropathy. In view of the
recently reported high response rates with Bortezomib containing regimens (VD,
VRD, VCD, VTD, PAD) prior and after high-dose therapy, a regimen with
Carfilzomib combining less polyneuropathy with similar efficacy would be a
likely candidate for standard induction in the future. Equally, such regimen
could be used for short consolidation treatment after high-dose therapy
Study objective
To assess the feasibility and efficacy of Carfilzomib in combination with
Thalidomide and Dexamethasone in a phase II trial.
Study design
This trial will establish the feasibility and efficacy of Carfilzomib, in
combination with Thalidomide and Dexamethasone as an induction therapy prior to
therapy with High Dose Melphalan (HDM) and Autologous Stem Cell Transplantation
(ASCT) in previously untreated patients with Multiple Myeloma. Stem cell
harvest will be performed using high-dose Cyclophosphamide and standard G-CSF.
In addition, the efficacy of a short (4 cycles) post-transplant consolidation
schedule of Carfilzomib, in combination with lower dose Thalidomide and
Dexamethasone will be investigated. The study will be conducted as a Phase II
trial.
Fifty patients will be included in the study cohort. Molecular (FISH)
characterization and gene expression profiling of the myeloma tumor cells will
be performed at inclusion. All patients will be followed closely for toxicities
and response assessment, as indicated. After completion of treatment, all
patients will be followed two-monthly until relapse or progression.
Intervention
The treatment is composed of the standard therapy for patient with Multiple
Myeloma at first presentation. Instead of giving, in the consolidation &
induction phase, Thalidomide, Dexamethason and a third agent (i.e. Bortezomib)
, Carfilzomib will be administered in combination with Thalidomide and
Dexamethasone.
Study burden and risks
Carfilzomib has been given as monotherapy ans also in combination with
Lenalidomide and dexamethsone but not with this peticular antimyeloma standard
chemotherapy regimen. So unexpected toxicites are possible.
A *first-dose* effect has been seen, which is notable for fever, chills,
rigors, and/or dyspnea occurring during the evening following the first day of
infusion and an increase in creatinine on Day 2, which may be the clinical
sequelae of rapid tumor lysis and/or cytokine release.
At time of the normal bone marrow punctions a limited amount of extra bone
marrow will be collected via the same needle.
p.a. Groene Hilledijk 301
Rotterdam 3075 EA
NL
p.a. Groene Hilledijk 301
Rotterdam 3075 EA
NL
Listed location countries
Age
Inclusion criteria
- Patients with a confirmed diagnosis of multiple myeloma stage II or III according to the Salmon & Durie criteria;
- Age 18-65 years inclusive;
- WHO performance status 0-3 (WHO<=3 is allowed only when caused by MM and
not by co-morbid conditions);
- Negative urine pregnancy test at inclusion if applicable;
- Written informed consent.
Exclusion criteria
- Known intolerance of Thalidomide;
- Previous chemotherapy or radiotherapy except 2 cycles of Melphalan/Prednisone
or local radiotherapy in case of local myeloma progression;
- Severe cardiac dysfunction;
- Creatinine clearance <30cc/min;
- ANC < 1,0 x109/L, platelets < 75 x109/L, Hb < 4.9 mmol/L;
- Patients with neuropathy, CTC grade 3 or higher or grade 2 painful peripheral neuropathy;
- Patients with a history of active malignancy during the past 5 years with the
exception of basal carcinoma of the skin or stage 0 cervical carcinoma;
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-014922-40-NL |
| CCMO | NL29308.078.10 |